The present invention relates to use of biomarkers of dry eye disease, and use of the biomarkers for selection of subjects for treatment and treatment of dry eye disease.

The present invention relates to use of biomarkers of dry eye disease, and use of the biomarkers for selection of subjects for treatment and treatment of dry eye disease.

In one aspect, described herein is an intronic recognition element for splicing modifier (iREMS) that can be recognized by a compound provided herein. In another aspect, described herein are methods for modulating the amount of a product of a gene, wherein a precursor RNA transcript transcribed from the gene contains an intronic REMS, and the methods utilizing a compound described herein. More particularly, described herein are methods for modulating the amount of an RNA transcript or protein product encoded by a gene, wherein a precursor RNA transcript transcribed from the gene comprises an intronic REMS, and the methods utilizing a compound described herein. In another aspect, provided herein are artificial gene constructs comprising an intronic REMS, and uses of those artificial gene constructs to modulate protein production. In another aspect, provided herein are methods for altering endogenous genes to comprise an intronic REMS, and the use of a compound described herein to modulate protein produced from such altered endogenous genes.

A compound of Formula I, ##STR00001##
and its analogs are provided. Compositions that include Formula I can be used to inhibit human equilibrative nucleoside transporter 1, increase adenosine signaling and produce effects that include increasing antiviral activity, increasing antiparasitic activity, increasing alcohol tolerance, decreasing pain protecting from ischemia as well as many other conditions.

The invention describes ophthalmic pharmaceutical formulations comprising pharmaceutical ingredients to address DED symptoms. In one aspect of the invention, an ophthalmic pharmaceutical formulation comprises: 1) lubricity-promoting ingredient(s) such as those listed in the FDA over the counter (OTC) monograph for ophthalmics as demulcents and 2) surfactant(s) that solubilize lipids, assist in lubrication, and assist in easily spreading over hydrophobic surfaces; and/or 3) lipid and/or plant oil ingredient(s) that assist in film formation and the spreading of tear fluid while promoting (or at least not inhibiting) lubrication; and/or 4) mucoadhesive and viscosity promoting polymer(s) that demonstrate shear thinning flow behavior. The pharmaceutical ingredients and osmoprotectant/tonicity ingredients are combined with ingredients that provide direct to the eye nutritional support that is comprehensive in nature. The total nutritional approach uses metabolically important tear fluid amino acids, vitamins, and both fatty acids/triglycerides and sugar molecules as energy sources. The invention results in both improved eye health and improved dry eye patient comfort.

The invention describes ophthalmic pharmaceutical formulations comprising pharmaceutical ingredients to address DED symptoms. In one aspect of the invention, an ophthalmic pharmaceutical formulation comprises: 1) lubricity-promoting ingredient(s) such as those listed in the FDA over the counter (OTC) monograph for ophthalmics as demulcents and 2) surfactant(s) that solubilize lipids, assist in lubrication, and assist in easily spreading over hydrophobic surfaces; and/or 3) lipid and/or plant oil ingredient(s) that assist in film formation and the spreading of tear fluid while promoting (or at least not inhibiting) lubrication; and/or 4) mucoadhesive and viscosity promoting polymer(s) that demonstrate shear thinning flow behavior. The pharmaceutical ingredients and osmoprotectant/tonicity ingredients are combined with ingredients that provide direct to the eye nutritional support that is comprehensive in nature. The total nutritional approach uses metabolically important tear fluid amino acids, vitamins, and both fatty acids/triglycerides and sugar molecules as energy sources. The invention results in both improved eye health and improved dry eye patient comfort.

Some embodiments disclosed herein relate to a composition containing an effective amount of dietary nutrients. In some embodiments, ingestion of the composition provides one or more of the following benefits, or others, improved functioning of an environmentally stressed eye, increased tear flow from the lacrimal glands, improved quality of the lipid secretion from the meibomian glands (e.g., to improve tear breakup time), and augmented DHA fatty acid in the retina damaged by blue light. In some embodiments, the composition is configured to scavenge free radicals in the eye to prevent premature degradation of the visual functions.

Some embodiments disclosed herein relate to a composition containing an effective amount of dietary nutrients. In some embodiments, ingestion of the composition provides one or more of the following benefits, or others, improved functioning of an environmentally stressed eye, increased tear flow from the lacrimal glands, improved quality of the lipid secretion from the meibomian glands (e.g., to improve tear breakup time), and augmented DHA fatty acid in the retina damaged by blue light. In some embodiments, the composition is configured to scavenge free radicals in the eye to prevent premature degradation of the visual functions.

The present disclosure relates to methods of treating chronic conditions of the eye, such as dry eye disease and blepharitis, as well as to methods for increasing secretion of meibum. This disclosure also relates to formulations suitable for treating chronic conditions of the eye such as dry eye disease and blepharitis.

The present invention is directed to an ophthalmic emulsion. The emulsion has a unique combination of ingredients that promotes the stability of small oil droplets within the emulsion. The emulsion also includes a mucoadhesive polymer that aid in delivering a lipid to the ocular surface.